2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1q
2017
Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes. Cell Reports 2017, 20: 76-88. PMID: 28683325, PMCID: PMC5547898, DOI: 10.1016/j.celrep.2017.06.023.Peer-Reviewed Original ResearchConceptsAD transgenic mouse modelDisease pathologyMetabotropic glutamate receptor 5Allosteric modulationGlutamate receptor 5Alzheimer's disease pathologyTransgenic mouse brainSilent allosteric modulatorsTransgenic mouse modelBroad therapeutic windowMouse phenotypeAD interventionSynaptic depletionBrain slicesGlutamate signalingMouse modelTherapeutic windowAD phenotypeReceptor 5Mouse brainAllosteric modulatorsMemory deficitsCellular prion proteinPathological roleMGluR5